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Biomedical subjects

M Marshall

Publications and source records attributed to M Marshall.

At least 91 records · Page 5Linked to original sources
PubMed1998

A community needs assessment: the care needs assessment pack for dementia (CarenapD)--its development, reliability and validity.

OBJECTIVE: To develop and evaluate a multidisciplinary needs assessment tool for people with dementia living in the community and their carers. DESIGN: The measure was developed through applying a theory of need, generating content, consultation with potential users and refinement and evaluation. Validity was established incrementally through the development process. SETTING: The development and evaluation was conducted in a variety of settings, including multidisciplinary dementia community care teams, social work departments, day hospitals, and inpatient and residential care. PATIENTS: The evaluation included community patients with a formal diagnosis of dementia (N = 34) and consultation with a multidisciplinary group of potential users (N = 23). The development process included inpatients with a formal diagnosis of dementia (N = 157) and consultation with potential users (N = 170) from a range of professions including both health and social care. MEASURES: Interrater reliability was assessed using the kappa statistic. Social validity was estimated using a measure developed for this purpose as part of the development process. RESULTS: The evaluation of interrater reliability demonstrated that three-quarters of assessors agreed on at least 85% of items in the CarenapD. The kappa statistic demonstrated that agreement for 76.2% of items in the CarenapD was 'good' or better (ie kappa >0.75), for 12.4% of items it was 'fair' or 'moderate' (ie kappa 0.35-0.60) and for the remaining 12 (11.4%) items for which kappa could not be calculated there was low intra-item variance and high agreement (>90%). There was good evidence for social validity. CONCLUSIONS: The CarenapD is a reliable and valid multidisciplinary assessment of need for people with dementia living in the community and their carers.

Aged↗
PubMed1998

Assessing relatives' needs for psychosocial interventions in schizophrenia: a relatives' version of the Cardinal Needs Schedule (RCNS).

BACKGROUND: The methodology for measuring the needs of patients with severe mental illness is now well established through the MRC Needs for Care Assessment Schedule and its modification in the form of the Cardinal Needs Assessment. This paper reports the rationale and construction of a relatives' version of the Cardinal Needs Schedule and looks at preliminary data reporting on reliability and validity. METHODS: Potential problem areas for relatives were identified from the literature. The criteria determining Cardinal Needs for each problem included objective threshold, carer concern, and carer cooperation. The reliability of the Schedule was assessed in a study whereby 27 relatives of patients with established schizophrenic illness completed two Schedules administered by two independent raters within a short time period. RESULTS: The Schedule was acceptably reliable for most areas of need although there were some difficulties associated with the cooperation criteria. Concurrent measures of relatives and patients including EE, relative distress and patient psychopathology indicated that the Relatives' Cardinal Needs Schedule shows acceptable validity when used with a sample of 45 relatives. CONCLUSIONS: The paper suggests that the Schedule may prove to be a useful tool for both clinicians and researchers interested in establishing and evaluating family interventions.

Activities of Daily Living↗
PubMed1998

An in vitro system for the analysis of changes in depth distribution of diffusates in bacterial films.

No suitable technique exists which allows simultaneous analysis of time- and depth-dependent concentrations of all components of interest in single samples of intercellular fluid from dental plaque biofilms. We have developed an in vitro model which allows detailed study of these interactions by analysis of intercellular fluid and pH measurement at the film base. Compact, defined-depth films of Streptococcus mutans were formed in a micrometer-controlled, variable-depth well and bathed in synthetic saliva. Films exposed to synthetic saliva containing glucose for 2 min followed by clearance with glucose-free synthetic saliva gave typical 'Stephan-type' pH profiles. Intercellular fluid isolated from successive 200-microm-thick sections of 600-microm-deep films was analysed by ion chromatography. A concentration gradient of lactate, falling with depth, was measured. The experimental system described here, the first of its type to be described, can easily be used to analyse pH changes and the depth-dependent distribution of diffusates in a model bacterial film. Although this bacterial film is far removed from a natural biofilm, the apparatus has potential for the study of grown biofilms and is an important advance towards position-dependence analysis of diffusates in biofilms.

Analysis of Variance↗
PubMed1998

Design, testing, and results of an outcomes-managed approach to patients requiring prolonged mechanical ventilation.

BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.

Adult↗
PubMed1997

Heme compounds in dinosaur trabecular bone.

Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues.

Animals↗
PubMed1997

Tobacco prevention in the Federated States of Micronesia.

The impact of tobacco-related illnesses in the Federal States of Micronesia (FSM) is discussed and documented for the 1970-95 period using national government statistics and gleanings from the research literature. Based upon international data concerning tobacco-related morbidity and mortality it is estimated that 15% of 1993 FSM mortality was smoking-related and that tobacco use contributes heavily to the non-communicable diseases that are the leading causes of death there. Sources and brands of cigarettes sold in the four FSM states are noted, as is the fact that cigarettes ranked among the top five import commodities in dollar value in the mid-1980s and early 1990s. Trend data are provided on cigarette imports from 1984 to 1993, during which time FSM citizens spent over US$25.5 m on this legal drug. Brand-price survey data of cigarettes and selected foodstuffs are presented as part of a discussion of the economic opportunity costs of smoking. Tax revenues from cigarettes are recorded, as are the steps toward smoking prevention and tobacco control taken by the FSM government. The article concludes with suggestions for additional controls that might be implemented.

Journal Article↗
PubMed1997

Phosphorylation of Raf-1 serine 338-serine 339 is an essential regulatory event for Ras-dependent activation and biological signaling.

Activation of the Raf serine/threonine protein kinases is tightly regulated by multiple phosphorylation events. Phosphorylation of either tyrosine 340 or 341 in the catalytic domain of Raf-1 has been previously shown to induce the ability of the protein kinase to phosphorylate MEK. By using a combination of mitogenic and enzymatic assays, we found that phosphorylation of the adjacent residue, serine 338, and, to a lesser extent, serine 339 is essential for the biological and enzymatic activities of Raf-1. Replacement of S338 with alanine blocked the ability of prenylated Raf-CX to transform Rat-1 fibroblasts. Similarly, the loss of S338-S339 in Raf-1 prevented protein kinase activation in COS-7 cells by either oncogenic Ras[V12] or v-Src. Consistent with phosphorylation of S338-S339, acidic amino acid substitutions of these residues partially restored transforming activity to Raf-CX, as well as kinase activation of Raf-1 by Ras[V12] or v-Src. Two-dimensional phosphopeptide mapping of wild-type Raf-CX and Raf-CX[A338A339] confirmed the presence of a phosphoserine-containing peptide with the predicted mobility in the wild-type protein which was absent from the mutant. This peptide could be quantitatively precipitated by an antipeptide antibody specific for the 18-residue tryptic peptide containing S338-S339 and was demonstrated to contain only phosphoserine. Phosphorylation of this peptide in Raf-1 was significantly increased by coexpression with Ras[V12]. These data demonstrate that Raf-1 residues 338 to 341 constitute a unique phosphoregulatory site in which the phosphorylation of serine and tyrosine residues contributes to the regulation of Raf by Ras, Src, and Ras-independent membrane localization.

Amino Acid Sequence↗
PubMed1997

Problems in conducting economic evaluations alongside clinical trials. Lessons from a study of case management for people with mental disorders.

BACKGROUND: Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care. METHOD: Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial. RESULTS: At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86-1.38) for total costs; 1.12 (0.76-1.65) for state benefits, and 1.21 (0.61-2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant. CONCLUSIONS: Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy.

Case Management↗
PubMed1996

Oligomerization activates c-Raf-1 through a Ras-dependent mechanism.

The c-Raf-1 proto-oncoprotein is a Ras-GTP-regulated protein kinase that associates in situ with 14-3-3 proteins, which are naturally dimeric. In COS cells, recombinant Raf is found in oligomeric assemblies. To examine whether induced oligomerization can alter Raf kinase activity, sequences encoding the FK506-binding protein FKBP12 were fused to the amino terminus of c-Raf-1, introducing a binding site for FK506. Oligomerization of recombinant FKBP-Raf in situ, induced by the addition of the dimeric FK506 derivative FK1012A, activated Raf kinase activity at least half as well as epidermal growth factor (EGF). As with EGF, activation of FKBP-Raf by FK1012A is entirely Ras-GTP dependent. Thus oligomerization of Raf per se promotes Raf activation through a Ras-dependent mechanism.

Biopolymers↗
PubMed1996

N-terminal sequences contained in the Src homology 2 and 3 domains of p120 GTPase-activating protein are required for full catalytic activity toward Ras.

The p120 GTPase-activating protein (GAP) is a negative regulator of Ras, which has a central role in signal transduction pathways that control cell proliferation. p120 GAP accelerates the conversion of activated Ras-GTP to its inactive form, Ras-GDP, thereby inhibiting mitogenic signaling. To examine potential contributions of p120 N-terminal sequences to regulation of its C-terminal catalytic domain, we constructed deletion mutants lacking defined regions, including the variable hydrophobic region as well as the Src homology 2 (SH2) and 3 (SH3) domains. These mutant proteins were expressed in infected Sf9 insect cells from recombinant baculoviruses and assayed in vitro for their ability to stimulate the intrinsic GTPase activity of purified Ras. While deletion of the variable hydrophobic region had no effect on p120 GAP activity, deletion of the entire SH2/SH3/SH2 region severely impaired catalytic activity toward Ras. Deletion of individual SH2 and SH3 domains within this region partially inhibited p120 GAP activity. Moreover, p120 N-terminal sequences enhanced the Ras GTPase-stimulating activity of the neurofibromin GAP-related domain. These results demonstrate that sequences in the SH2/SH3/SH2 region of p120 GAP are required for full catalytic activity toward Ras. Together with earlier findings that the p120 GAP SH2 domains mediate interactions with several GAP-associated proteins, our results suggest multiple roles for the N-terminal sequences in regulating p120 GAP catalytic activity and mitogenic signaling pathways. In addition, our results raise the possibility that SH2 domain point mutations in p120 GAP detected in some basal cell carcinomas reduce catalytic activity toward Ras and thereby contribute to oncogenesis.

Animals↗
PubMed1996

A new method of intralesional bleomycin therapy in the treatment of recalcitrant warts.

We have used a new technique of bleomycin injection to treat intractable palmar, plantar and periungual warts. Following local anaesthesia with topical EMLA (lignocaine and prilocaine) cream, 1 mg/ml bleomycin solution was dropped on to the wart and 'pricked' into the wart using a Monolet needle. We achieved 92% success rate which compares well with other authors whose success rates with intralesional bleomycin vary between 33 and 92%. We conclude that this technique of intralesional bleomycin therapy is an effective, safe and generally well tolerated treatment for recalcitrant warts.

Adolescent↗